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- Title
Site-specific GlcNAcylation of human erythrocyte proteins: potential biomarker(s) for diabetes.
- Authors
Wang Z; Park K; Comer F; Hsieh-Wilson LC; Saudek CD; Hart GW; Wang, Zihao; Park, Kyoungsook; Comer, Frank; Hsieh-Wilson, Linda C; Saudek, Christopher D; Hart, Gerald W
- Abstract
<bold>Objective: </bold>O-linked N-acetylglucosamine (O-GlcNAc) is upregulated in diabetic tissues and plays a role in insulin resistance and glucose toxicity. Here, we investigated the extent of GlcNAcylation on human erythrocyte proteins and compared site-specific GlcNAcylation on erythrocyte proteins from diabetic and normal individuals.<bold>Research Design and Methods: </bold>GlcNAcylated erythrocyte proteins or GlcNAcylated peptides were tagged and selectively enriched by a chemoenzymatic approach and identified by mass spectrometry. The enrichment approach was combined with solid-phase chemical derivatization and isotopic labeling to detect O-GlcNAc modification sites and to compare site-specific O-GlcNAc occupancy levels between normal and diabetic erythrocyte proteins.<bold>Results: </bold>The enzymes that catalyze the cycling (addition and removal) of O-GlcNAc were detected in human erythrocytes. Twenty-five GlcNAcylated erythrocyte proteins were identified. Protein expression levels were compared between diabetic and normal erythrocytes. Thirty-five O-GlcNAc sites were reproducibly identified, and their site-specific O-GlcNAc occupancy ratios were calculated.<bold>Conclusions: </bold>GlcNAcylation is differentially regulated at individual sites on erythrocyte proteins in response to glycemic status. These data suggest not only that site-specific O-GlcNAc levels reflect the glycemic status of an individual but also that O-GlcNAc site occupancy on erythrocyte proteins may be eventually useful as a diagnostic tool for the early detection of diabetes.
- Publication
Diabetes, 2009, Vol 58, Issue 2, p309
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db08-0994